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Salmonella contamination in pig slaughterhouses is linked to infection rate on farms. Accurate diagnosis in heavy pigs relies on isolating pathogens from the gut wall or lymph nodes. A key technique is Immunocapture using Magnetic Beads (IMS), which purifies target bacteria from Salmonella enrichment broths. This is followed by an Enzyme-Linked Immunomagnetic Electrochemical (ELIME) assay for rapid detection. In our study, we developed an ELIME-IMS hybrid assay to detect Salmonella in swine mesenteric lymph nodes (MNL), involving a clean-up with N-acetylcysteine and centrifugation. Detection limits for S. Typhimurium and S. Derby were estimated at 2.80 and 3.52 Log CFU/ml, respectively. We analysed 103 MNL samples from a northern Italy slaughterhouse. Additionally, we examined 15 carcass swabs. Both the ELIME assay and the IMS-based culture method showed strong agreement with the ISO 6579-1:2017 method, especially after 20 h of enrichment (89.47% concordance). The clean-up step significantly influenced the results, as samples processed without it showed higher variability. A logistic regression model indicated high classification accuracy for negative samples using ELIME values. The ELIME-IMS assay facilitates rapid Salmonella screening and isolation in swine mesenteric lymph nodes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To explore the similarities and differences of organization-based and informal spotting (remote supervision of substance use) from the perspectives of spotters and spottees across Canada., Methods: Spotters and spottees who spot informally and for organizations were recruited across Ontario and Nova Scotia. We interviewed 20 informal and 10 organization-based participants by phone using semi-structured interviews between 08/2020 and 11/2020. Participants were asked about each methods benefits and limitations. Interviews were audio-recorded, transcribed, and analyzed thematically., Results: Benefits of informal spotting included its ability to strengthen social connections and foster autonomy in overdose response planning. The lack of support for informal spotters created stress and burnout. Organization-based spotters enjoyed the spotting training and support provided. However, regulations surrounding having to call ambulance in overdose events deterred many people from wanting to work for or call these services., Conclusions: Both organization-based and informal spotting have a role in mitigating harms associated with the overdose crisis. Moving forward, further research is needed on how to optimize these services for all people who use drugs in varying jurisdictions internationally., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

The COVID-19 pandemic has increased the uptake of virtual and remote service delivery in the substance use field, which was previously uncommon. This swift uptake of virtual services provides an opportunity to improve service design to meet the diverse needs of women and gender-diverse people. Such services have the potential to better meet the needs of women and gender-diverse people by allowing for increased choice, control, and autonomy, enabling empowerment, facilitating greater considerations of power relations, violence, childcare responsibilities, and fostering greater inclusion of trans and non-binary people. This commentary aims to identify how virtual and remote delivery of substance use treatment and harm reduction services can be gender-responsive. We highlight the role gender transformative services play in meeting the unique needs of women and gender-diverse people who use drugs both during and after the COVID-19 pandemic. By using the unique window of opportunity COVID-19 has created to develop and deliver gender-transformative programs, we can help address the detrimental gaps in service accessibility and effectiveness that have persistently been experienced by women and gender-diverse people who use drugs., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Immune checkpoint inhibitors (ICIs) have completely reshaped the treatment of many malignancies, with remarkable improvements in survival outcomes. In ovarian cancer (OC), however, this emerging class of drugs has not yet found a favorable use due to results from phase I and II studies, which have not suggested a substantial antitumoral activity of these agents when administered as monotherapy. Robust preclinical data seem to suggest that the combination ICIs with poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) may result in a synergistic activity; furthermore, data from phase II clinical studies, evaluating this combination, have shown encouraging outcomes especially for those OC patients not suitable for platinum retreatment. While waiting for ongoing phase III clinical trial results, which will clarify the role of ICIs in combination with PARPis in the newly diagnosed OC, this review aims to summarize the preclinical data and clinical evidence available to date., Competing Interests: Disclosure DL reports research funding from Clovis, GSK, and MSD; personal interests with AstraZeneca, Clovis Oncology, GSK, PharmaMar, MSD; and financial interests with Clovis, Genmab, GSK, MSD. He also serves on the Board of Directors of GCIG (Gynecologic Cancer Inter Group). VS reports honoraria from GSK, PharmaMar, Roche, MSD, EISAI, Clovis, Oncology, and AstraZeneca. GS reports research support from MSD and honoraria from Clovis Oncology; serves as a consultant for Tesaro and Johnson & Johnson. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Disability faced by a young person can impact the school-to-work transition and shape health and well-being over the life course. Unique barriers to entry and advancement within the labor market that are relevant to young people with disabilities underscore the need for tailored policy-level supports., Objectives: To examine and describe policies that support the school-to-work transition of young people with disabilities in Canada., Methods: A scan of policies which focused on the school-to-work transition of young people with disabilities across Canada was conducted between June 2019 and January 2020. Searches were completed within federal, provincial and territorial policy portals. Each policy relating to employment participation of people with disabilities was summarized. Policies that focused on the school-to-work-specific were synthesized using Bemelmans-Vidic, Rist and Vedung's policy tool framework., Results: A total of 36 policies were identified by our scan that focused on the employment of people with disabilities. Only five policies explicitly addressed the school-to-work transition. All existing policies were implemented at the provincial level and aimed to promote entry into employment. The synthesis of policies revealed that financial policy tools were primarily used to incentivize employment, provision of workplace accommodations, or the development and implementation of job readiness programs., Conclusion: Our analysis of federal, provincial and territorial policies in Canada uncovered a limited number of policies that specifically support the school-to-work transition. Addressing these policy gaps can increase the inclusion of young people with disabilities in the labor market., Competing Interests: Conflicts of interest No conflicts of interest related to this research to support., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: People who use drugs (PWUD), and especially those who inject drugs, are at increased risk of acquiring bloodborne infections (e.g., HIV and HCV), experiencing drug-related harms (e.g., abscesses and overdose), and being hospitalized and requiring inpatient parenteral antibiotic therapy delivered through a peripherally inserted central catheter (PICC). The use of PICC lines with PWUD is understood to be a source of tension in hospital settings but has not been well researched. Drawing on theoretical and analytic insights from "new materialism," we consider the assemblage of sociomaterial elements that inform the use of PICCs., Methods: This paper draws on n = 50 interviews conducted across two related qualitative research projects within a program of research about the impact of substance use on hospital admissions from the perspective of healthcare providers (HCPs) and people living with HIV/HCV who use drugs. This paper focuses on data about PICC lines collected in both studies., Results: The decision to provide, maintain, or remove a PICC is based on a complex assemblage of factors (e.g., infections, bodies, drugs, memories, relations, spaces, temporalities, and contingencies) beyond whether parenteral intravenous antibiotic therapy is clinically indicated. HCPs expressed concerns about the risk posed by past, current, and future drug use, and contact with non-clinical spaces (e.g., patient's homes and the surrounding community), with some opting for second-line treatments and removing PICCs. The majority of PWUD described being subjected to threats of discharge and increased monitoring despite being too ill to use their PICC lines during past hospital admissions. A subset of PWUD reported using their PICC lines to inject drugs as a harm reduction strategy, and a subset of HCPs reported providing harm reduction-centred care., Conclusion: Our analysis has implications for theorizing the role of PICC lines in the care of PWUD and identifies practical guidance for engaging them in productive and non-judgemental discussions about the risks of injecting into a PICC line, how to do it safely, and about medically supported alternatives., Competing Interests: Declarations of Interest None., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of the study was to examine the need for modified safety planning strategies in response to COVID-19-related increases in intimate partner violence (IPV) as the initial phase of adapting an IPV safety planning intervention in Toronto, Ontario., Methods: A rapid, systematic review was conducted to elucidate existing safety planning strategies used during public health emergencies. These were supplemented with strategies from an expert panel. A survey of IPV survivors and service providers gauged the helpfulness of each strategy during COVID-19., Results: Together, the systematic review and expert panel yielded 26 conceptually distinct strategies, which were evaluated by 111 IPV survivors and providers. Of these, 19 (69%) were 'highly recommended', 3 (12%) were 'somewhat recommended' and 6 (23%) were not recommended for use during the COVID-19 pandemic because they might make the violence worse., Conclusions: Safety planning needs have changed owing to the effect of COVID-19 on IPV incidence, service provision and risk factors, as well as policies restricting freedom of movement. These results will be used to modify an existing IPV safety planning mobile application for use during COVID-19 and future public health emergencies., (Copyright © 2021 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Current rates of opioid-related mortality have been increasing globally. An effective harm reduction program consists of overdose education and naloxone distribution (OEND) programs. Incorporating both education and naloxone administration, OENDs have been reported to improve knowledge, self-efficacy and have resulted in multiple overdose reversals. Similarly effective has been the incorporation of Behaviour Change Theories within harm reduction programs. Although limited, literature that does exist surrounding this intersection, explains how theories such as social cognitive theory and the transtheoretical model have proven to reduce harms relating to injection drug use. Engaging with participants at multiple levels while using a context-dependent and iterative approach have been documented strengths of behaviour change theories with respect to minimizing substance use behaviours. This commentary argues for the potential benefit, incorporating behaviour change theories in OENDs has in reducing opioid-related overdoses., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To provide a comprehensive comparative evaluation of the psychometric properties of satisfaction with medication surveys used for patients with type 2 diabetes (T2D) in clinical trials., Methods: Instruments identified through a comprehensive literature search were evaluated based on the following criteria: disease specificity, peer-reviewed publication (administered in English in patients with T2D on oral therapy), and availability of psychometric properties., Results: Eight instruments (Diabetes Medication Satisfaction [DiabMedSat]; Diabetes Treatment Satisfaction Questionnaire, status version [DTSQs]; Diabetes Medication System Rating Questionnaire [DMSRQ]; Diabetes Medication System Rating Questionnaire-Short Form [DMSRQ-SF]; Diabetes Tablet Treatment Questionnaire [DTTQ]; Perceptions About Medications for Diabetes [PAM-D]; Satisfaction with Oral Anti-Diabetic Agent Scale [SOADAS]; Diabetes Medication Satisfaction Tool [DMSAT]) were included in the study based on the predefined inclusion criteria. Seven of the instruments (all but DTTQ) utilized patients in the survey development process. All eight instruments could be completed within 15 minutes and thus were considered practical. DiabMedSat, DMSRQ, and DMSRQ-SF encompassed broader aspects of satisfaction than the other instruments. All of the instruments reviewed showed substantial floor or ceiling effects, except for DMSAT and DiabMedSat, without complete information. The DMSRQ and DMSRQ-SF each satisfied the criteria for reliability. DiabMedSat, DTSQs, DMSRQ, DMSRQ-SF, SOADAS, and DMSAT showed favorable convergent and discriminant validity. All of the instruments except DTTQ were determined to satisfactorily meet the criteria of responsiveness., Conclusion: Although it is up to researchers to decide which instrument to use according to the resources available and specific aims of their studies, DMSRQ and DSMRQ-SF were recommended based on the evaluative criteria employed in this study., (Copyright © 2018 ISPOR--The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Introduction: In 2016, new Accreditation Standards were implemented that required integration of affective domain elements (ADEs) into the Doctor of Pharmacy (PharmD) curriculum and admissions interview process. The purpose of this study is to analyze the relationship between admissions variables and performance in a new course, and to analyze the relationship between student self-assessment and faculty evaluation of their development and performance in ADEs., Methods: Pre-pharmacy admission variables were evaluated for correlations with student performance in ADEs. Student self-assessments and faculty evaluations of performance in ADEs were also analyzed., Results: Statistically significant positive correlations were found between student age and completion of at least a bachelor's degree with student self-assessment in communication and leadership. When evaluating faculty assessment, significant positive correlations were found for female performance in the areas of leadership and team readiness. There was a positive association between the Pharmacy College Admission Test (PCAT) quantitative score and performance in professionalism; while negative associations were seen between the PCAT comprehensive score and student self-assessment in self-awareness and professionalism, and between the PCAT quantitative score and student self-assessment in self-awareness (p < 0.05 for all). Median evaluation ranks by faculty members were significantly lower than the median self-evaluation ranks done by students., Discussion and Conclusion: This study suggests careful analysis of admissions variables in relation to ADEs may offer PharmD programs insight into how they design educational activities related to the affective domain. Additionally, evaluating multiple observations by both students and faculty members may identify patterns of growth and development in ADEs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Vascular medicine is now a clinical specialty in France. During their studies, students will acquire clinical reasoning in addition to technical skills. An Objective Structured Clinical Examination (OSCE) is considered as the gold standard for evaluating clinical competence. Our main objective was to evaluate the feasibility and acceptability of OSCE for the evaluation of students, secondarily their performance., Methods: Three representative clinical cases of the specialty were developed. The OSCE consisted of a sequence of clinical situations presented in three stations of 7minutes each. The role of the simulated patient was played by medical students. At the end of the OSCE, observers and students completed the evaluation form. We compared the performances between junior and senior vascular medicine students. Written questionnaires were used to measure OSCE satisfaction., Results: We were able to develop and organize this examination without difficulties. Fifteen students were evaluated. All participants agreed that the clinical situations were representative of vascular medicine practice, the cases were realistic and standardized patients were convincing. The performance of senior students was statistically higher than junior students in one case., Discussion: Our study demonstrates the feasibility and acceptability of the OSCE in students in vascular medicine. The small number of stations and candidates requires further studies on a larger scale to evaluate their performance., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

We describe the case of a 75-year-old woman presenting with spotted fever followed by acute renal failure and septic shock. The infection was caused by Rickettsia typhi, not reported in Calabria district (southern Italy) since World War II. The diagnosis of murine typhus was made 3 days after admission and was based solely on clinical criteria when her worsening condition required a prompt move to the intensive care unit. Therapy with tigecycline was then started immediately and the patient improved dramatically. The diagnosis of murine typhus was confirmed 10 days after admission by immunofluorescence assay. Our case is an example of how the diagnosis of murine typhus is challenging. However, in the case of a disease lacking specific symptoms, clinicians should never forget that, even in geographic areas considered free of flea-borne diseases, the components of the enzootic cycle are present and the diagnosis should never be underestimated., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ligand activation of peroxisome proliferator-activated receptor (PPAR)gamma and retinoid X receptor (RXR) induces antitumor effects in cancer. We evaluated the ability of combined treatment with nanomolar levels of the PPARgamma ligand rosiglitazone (BRL) and the RXR ligand 9-cis-retinoic acid (9RA) to promote antiproliferative effects in breast cancer cells. BRL and 9RA in combination strongly inhibit of cell viability in MCF-7, MCF-7TR1, SKBR-3, and T-47D breast cancer cells, whereas MCF-10 normal breast epithelial cells are unaffected. In MCF-7 cells, combined treatment with BRL and 9RA up-regulated mRNA and protein levels of both the tumor suppressor p53 and its effector p21(WAF1/Cip1). Functional experiments indicate that the nuclear factor-kappaB site in the p53 promoter is required for the transcriptional response to BRL plus 9RA. We observed that the intrinsic apoptotic pathway in MCF-7 cells displays an ordinated sequence of events, including disruption of mitochondrial membrane potential, release of cytochrome c, strong caspase 9 activation, and, finally, DNA fragmentation. An expression vector for p53 antisense abrogated the biological effect of both ligands, which implicates involvement of p53 in PPARgamma/RXR-dependent activity in all of the human breast malignant cell lines tested. Taken together, our results suggest that multidrug regimens including a combination of PPARgamma and RXR ligands may provide a therapeutic advantage in breast cancer treatment.

Frontotemporal dementia (FTD) is a complex dementing syndrome whose genetic/non genetic risk factors are mostly unknown. Aim of the present work was to investigate whether APOE and/or tau gene variability does affect the risk of FTD. A sample of FTD cases (sporadic: n = 54; familial: n = 46, one subject per family) was collected in a genetically homogeneous population (Calabria, southern Italy) and analyzed in comparison with an age- and sex-matched control group (n = 180) extracted from the same population. Logistic regression analysis showed that APOE gene variability affects the probability of disease, with allele epsilon4 increasing (exp(beta1) = 2.68 with [1.51-4.76] 95% confidence interval; p = 0.001) and allele epsilon2 decreasing (exp(beta1) = 0.28 with [0.12-0.66] 95% confidence interval; p = 0.003) the risk of FTD. On the contrary, tau gene variability was ineffectual (exp(beta1) non significantly different from 1 for either H1 or H2 haplotypes), although a small effect was observed by the H1 haplotype in increasing the protective effect of the epsilon2 allele (p = 0.007).

Objective: To evaluate the level of agreement among three previously validated self-reported medication adherence measures and pharmacy refill records (RRs)., Design: Cross-sectional study., Setting: Five primary care physician office sites in rural northeast Georgia., Participants: 139 adult patients with one or more of these chronic diseases: hypertension, diabetes mellitus, hypercholesterolemia, hypothyroidism, or a condition requiring hormone replacement therapy., Interventions: Study participants completed the Brief Medication Questionnaire (BMQ), the Medication Adherence Survey (MAS), and the Medical Outcomes Study (MOS) instruments; pharmacy RRs for the medication or medications being used to treat the target disease were obtained from pharmacies used by the study participants., Main Outcome Measures: Adherence to medication therapy for target disease., Results: Participants were nearly all white (98.6%), consistent with the Appalachian area in which the study was conducted, and mostly women (71.9%). While 91.4% of study participants reported taking their study medication most or all of the time, RRs showed mean adherence rates of 82.6%, 82.1%, 79.1%, 74.6%, and 69.8% for diabetes mellitus, hypertension, hypothyroidism, hypercholesterolemia, and hormone replacement therapy, respectively. Moderate correlations of .234, .261, and .213 were found between RRs and the MAS, MOS, and BMQ belief screen, respectively. Spearman correlations ranged from .091 between RRs and the BMQ regimen subscale to .313 between MOS and MAS. Pearson chi-square tests showed that only the BMQ belief subscale was significant in this study., Conclusion: Because of the weak to moderate concordance found among validated measures of adherence, the selection of a useful adherence measure in pharmacy practice is difficult. These findings underscore the difficulty in both assessing patients' medication-taking behavior and assessing and comparing the results of adherence research. The development of valid and reliable measures for easily assessing medication adherence behavior in community pharmacies is needed.

Adherence determinants and key adherence research issues are discussed for three types of randomized controlled trials: pharmacological, dietary, and physical activity. This article highlights theoretical and methodological limitations that have hampered the ability to identify patients at risk for poor treatment compliance. Control Clin Trials 2000;21:195S-199S

This paper reviews issues regarding dietary adherence. Issues and barriers unique to dietary adherence, in contrast to adherence to physical activity or medication regimens, are discussed. These include decision making, social and cultural contexts, perceptions and preferences, and environmental barriers. We review factors known to increase adherence in dietary interventions, including education, motivation, behavioral skills, new and modified foods, and supportive interactions. We conclude with directions for future study, such as improved measurement of diet-related behavior and longitudinal, culturally sensitive interventions. Control Clin Trials 2000;21:206S-211S

Objectives: To determine the carriage rate of Staphylococcus aureus (SA), both methicillin sensitive, and methicillin resistant (MRSA), among employees of a nursing home in the absence of an epidemic., Design: Observational study., Setting: A 210-bed suburban skilled nursing facility with a low endemic rate of SA infection., Participants: Seventy-three asymptomatic employees recruited in two waves., Measurement: Nasal swabs were cultured for SA; DNA strain typing was performed on MRSA isolates from the first wave of recruits., Results: 21 of 73 (29%) cultures were positive for SA. Ten of these 21 (14% of participating employees) had nasal carriage of MRSA. MRSA carriage was not significantly correlated with age, duration of employment, or job type (clinical vs. non-clinical), and DNA strain typing suggested that employee carriage of MRSA was not the result of a common source., Conclusions: Staphylococcus aureus nasal carriage is common among skilled nursing facility personnel, and MRSA accounts for a substantial proportion of SA carriage among employees, even in the absence of an epidemic. Further research is needed to determine whether the high SA carriage rates among employees reflects work place acquisition, and, if so, whether it poses a hazard to the employees. The low incidence of nosocomial MRSA infections around the time of the study suggests that with usual infection control practices (eg, hand washing), MRSA-colonized caregivers pose little risk to nursing facility residents.

In this study, the authors describe the psychological characteristics of a large sample (N = 407) of adult patients evaluated for liver transplantation, and provide normative data on commonly used measures of cognitive functioning, affective status, psychosocial adjustment, coping, quality of life, and life satisfaction. The normative data suggest that the study's liver transplant candidates have poorer cognitive functioning and health-related quality of life when compared with available normative comparison groups, yet the former group is more comparable to medically ill peers on measures of anxiety, depression, psychosocial adjustment, and coping. Data also suggest a high rate of affective disturbance in liver transplant candidates. Results indicate the utility of normative data, such as the authors', for providing an appropriate comparison group for liver pretransplant candidates.

The relationship between one of Andersen's enabling factors, health insurance status and the choice of a pharmacist as the initial contact in the health care system was examined via telephone surveys. Eighty-seven percent of the sample reported having some form of health insurance. Of all intended health care provider contacts, pharmacists were selected as the initial contact 21% of the time. Logistic regression identified insurance status, education and race as significant (alpha < 0.05) covariates in the model. The odds ratios generated from the logit model indicated that non-whites, persons with less education and no health insurance were more likely to select a pharmacist for triage. The study concluded that uninsured persons were nearly twice as likely to seek pharmacist triage than insured individuals. Pharmacists may be filling an important triage gap for individuals who have limited financial access to traditional sources of physician care.

Objective: We sought to find a combination of noninvasive treatments for snoring by adding weight loss to previously studied treatments, including the combination of sleeping on one's side and using a decongestant nasal spray., Study Population: Twenty asymptomatic men who snore heavily were studied previously on a control night and on a night when they slept on their side and used a nasal spray. With these two treatments, minor improvements in apnea/hypopnea index (AHI) were seen, but no improvement occurred in snoring frequency. Nineteen of these subjects subsequently completed a 6-month weight loss program, and 12 lost weight. These 19 subjects comprise the study population of this report., Study Design: At the conclusion of the weight loss program, a repeated sleep study was done from which the effect of adding weight loss to the two previously studied treatments could be assessed., Results: Those 12 subjects who lost any amount of weight showed a very mild reduction in snores per hour from 328 using two modalities of treatment to 232 per hour with the addition of weight loss (p = 0.15). The nine subjects who lost > or = 3 kg reduced the number of snores per hour from 320 to 176 (p = 0.0496). Three subjects losing an average of only 7.6 kg showed virtual elimination of snoring after weight loss. Subjects who gained weight had no improvement in snoring. Weight loss added to the other two modalities of treatment had no effect on the AHI., Conclusion: In most cases, the combination of weight loss, sleeping on one's side, and the administration of a nasal decongestant significantly reduces the frequency of snoring in asymptomatic men who snore heavily. The major effect appears to be related to weight loss.

A new substrate optimized assay for acyl-CoA:cholesterol acyltransferase (ACAT) was developed that permits the accurate measurement of ACAT activity in normal arterial microsomes. The apparent Km and Vmax of ACAT with respect to oleoyl-CoA were determined to be 3 microM and 17.7 pmole min-1 mg-1. While the Km value is similar to other values reported in the literature, the Vmax is 5- to 8-fold higher. The higher Vmax is attributable to the saturation of ACAT with not only oleoyl-CoA, but also cholesterol. The observation that exogenous cholesterol was necessary for the determination of maximal ACAT activity indicates that under normal conditions the endogenous level of microsomal cholesterol does not saturate ACAT. Assay of ACAT in the presence and absence of exogenous cholesterol permits a qualitative assessment of the amount of cholesterol in the cholesterol substrate pool of ACAT. Using this approach, it was found that hypercholesterolemia results in the expansion of the cholesterol substrate pool of ACAT. Of the 21-fold increase in ACAT activity in atherosclerotic aortas observed in this study. 80% of the increase was attributable to expansion of the cholesterol substrate pool, while 20% was attributable to more enzyme. Notably, the increase in the amount of ACAT was observed after only 2 weeks of hypercholesterolemia.

Ammonium perfluorooctanoate (APFO) is known to induce a striking hepatomegaly in rats. The purpose of these studies was to determine the causes of the hepatomegaly and compare the effect to other liver-enlarging compounds. Since the total hepatic DNA content was similar in control and APFO-treated rats, the hepatomegaly represented a hypertrophic rather than a hyperplastic response. The cytochrome P-450 content and activity of benzphetamine N-demethylase increased in the livers of APFO-treated rats, indicating the proliferation of the smooth endoplasmic reticulum. In contrast to the membrane-bound enzymes, the soluble enzymes glutathione S-transferase and UDPglucuronyltransferase were unaffected by APFO treatment. The activity of carnitine acetyltransferase was disproportionately increased relative to carnitine palmitoyltransferase in the livers of APFO vs that in control rats, confirming the predominant proliferation of peroxisomes vs that of mitochondria. Morphological studies confirmed the proliferation of the endoplasmic reticulum, mitochondria, and peroxisomes in the livers of APFO-treated rats. In contrast to many other peroxisome proliferating agents, APFO did not possess hypolipidemic activity.